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Journal of Environmental Pathology, Toxicology and Oncology
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ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2013006843
pages 91-99

Cellular Internalization and Mechanism of Cytotoxicity of 131I-Rituximab in Raji Cells

Chandan Kumar
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India
Badri Narain Pandey
Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India
Grace Samuel
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India
Meera Venkatesh
Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India

ABSTRAKT

Rituximab labeled with radioiodine (131I-rituximab) has a large potential to be employed for targeted therapy of non-Hodgkin's lymphoma. Studies of parameters such as cellular internalization, stability of 131I-rituximab bound to CD20 receptor of tumor cells, and the mechanism underlying cytotoxicity induced by 131I-rituximab will be useful for better clinical application. In this article we describe the efficacy of 131I-rituximab in CD20-expressing Raji cells. Rituximab labeled with 131I was purified on a PD-10 column and characterized using high-performance liquid chromatography and paper electrophoresis. Raji cells treated with 131I-rituximab (1.85 MBq for 2 hours) were washed then incubated. The culture medium collected from treated cells showed increased radioactivity over a longer period (>6 hours), probably due to the deiodination/degradation of 131I-rituximab. The tumor cells treated with 131I-rituximab showed time-dependent internalization of radioactivity, and at 12 hours the radioactivity was almost equally distributed in the membrane and cytoplasm. At 24 hours ~70% of the radioactivity was internalized. Cellular toxicity after 131I-rituximab treatment showed a time-dependent increase in toxicity as estimated by lactate dehydrogenase. Tumor cells treated with 131I-rituximab showed significantly higher toxicity and apoptosis compared with the those treated with the same concentration of unlabeled rituximab. The increased apoptotic death in cells treated with 131I-rituximab was associated with cleavage of poly ADP ribose polymerase and upregulation of p53 protein. This study provides a deeper understanding about the cellular internalization/stability of 131I-rituximab bound to the CD20 receptor and its efficacy in killing Raji cells.


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